Riociguat is chemically described as Methyl N-[4,6-Diamino-2-[1-[(2-fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl]-N-methyl-carbamate represented by structural Formula I.

Riociguat is the first of a new class of Guanylatecyclase (sGC) agonists, which directly activates sGC and increases low levels of NO sensitivity, for treating pulmonary hypertension and chronic obstructive pulmonary hypertension.
U.S. Pat. No. 7,173,037 discloses a preparation method of the compound of Formula I wherein the compound of Formula I is obtained by recrystallization from methanol.
US20110130410 disclose a DMSO solvate of the compound of Formula I.
WO2015055124 A1 discloses crystalline form I, form II, form III, form IV, and an amorphous form of the compound of Formula I.
WO2003095451A1 discloses a preparation method of the compound of Formula I as shown below in scheme I.

WO2011064171A2 also discloses a preparation method of the compound of Formula I as shown below in scheme 2.

Synthesis and purification as reported in WO2003095451A1 have a number of disadvantages which are very unfavorable for industrial realization on a large scale. This is true especially for the isolation of the trisamino compound as trihydrochloride of the compound of formula (IV). The addition of hydrochloric acid requires an acid-proof industrial plant, and the yield of the step is only an unsatisfactory 59.3% of theory (see, for example, Example 8A of WO 03/095451). The realization of the reaction of the trisamino compound of formula (IV) or the corresponding HCl-free base in the solvent pyridine is likewise disadvantageous. The compound of formula (VI) can only be isolated by complete evaporation of the reaction mixture, which is disadvantageous on an industrial scale (see, for example, Example 5 of WO 03/095451). On a relatively large scale, such steps generally result in considerable problems such as sticking-on or thermal decomposition owing to the substantially longer thermal stress when a reaction is carried out on a relatively large scale. The purification of the product represented by formula (VI) according to the experimental procedure of Example 5 from WO 03/095451 by boiling in diethyl ether also has considerable disadvantages. Because of the high flammability of diethyl ether, this step can be realized only with increased industrial expenditure.
However, particularly disadvantageous are the purification processes for the crude product of the formula (I). An effective purification is a condition sine qua non for use as a pharmaceutically active compound. The described purification via RP HPLC, i.e. the chromatographic purification, is a laboratory method, the realization of which on an industrial scale is very expensive. In addition, the stated yield of only 29% for the synthesis step to the crude product of the formula (I) and its purification is very low. The alternative preparation and purification method is very complicated. It comprises a total of 5 isolations of solids (2 concentrations to dryness and 3 filtrations), and, as already mentioned above, concentrations to dryness on an industrial scale are very unfavorable. Altogether, when carrying out a chemical step, a number of 5 isolations of solids for the preparation and purification of a pharmaceutically active compound on an industrial scale is very disadvantageous.
It has been the endeavor of pharmaceutical scientists to provide novel and stable forms of drug substances, which would have the strengths of thermodynamic stability, enhanced solubility, rapid onset of action and an enhanced bioavailability. However, it is well known in the art that polymorphism is unpredictable, both as regards the uncertainty that any new forms will be found, and the lack of any standard methods for preparing a new form. This has been discussed in the literature, such as A. Goho, “Tricky Business,” Science News, Vol. 166(8), Aug. 21, 2004, and A. M. Rouhi, “The Right Stuff,” Chemical and Engineering News, Feb. 24, 2003, pages 32-35.
Therefore, it would be desirable to provide stable polymorph of Riociguat and processes for their preparation, which are commercially viable. Another object to provide a simplified process which is safe and can also be carried out advantageously on an industrial scale and which supports an active compound in high yield and high purity in pharmaceutically acceptable quality.